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CATARACT-THE ULTRAVIOLET RISK FACTOR
1249 CATARACT-THE ULTRAVIOLET RISK FACTOR DAVID MORAN
FRED HOLLOWS
Department of Ophthalmology, Prince of Wales Hospital/University of New South Wales, Australia
Ophthalmic examination of 64 307 Aborigines and 41 254 non-Aborigines in remote rural Australia during the course of the National Trachoma and Eye Health Program revealed a positive correlation between the prevalence of senile cataract and levels of climatic ultraviolet (UV) radiation. Aborigines were more likely to be affected by senile cataract than nonAborigines. It seems that Aborigines who live in areas of higher UV irradiation are more likely to acquire cataract; more likely to acquire the condition earlier in life; and more likely to be blind or visually disabled by it, than their counterparts living in areas of low UV irradiation. Provision of adequate shelter in areas of high insolation, where most cases of cataract occur, is likely to be an effective preventive Summary
measure.
Introduction NEAR ultraviolet (UV) light is able to induce opacity of the crystalline lens, both in vivo and in vitro. This process probably involves the photoxidation of aromatic aminoacids, particularly tryptophan. n2 The effect seems to be cumulative and is inhibited by physiological levels of ascorbate and glutathione, a fact which provides an enticing clue to the specific functions of these two substances in the lens. Our data on more than 105 000 people examined in more than 400 centres throughout the more remote parts of the Australian continent presented an opportunity to assess cataract prevalence and effects in the two major racial groups living in a range of different zones of UV irradiation. Methods
Ophthalmologists from the National Trachoma and Eye Health Program examined 64 307 Aborigines and 41 254 non-Aborigines during the course of three years’ fieldwork. An attempt was made to obtain a thorough coverage of the Aboriginal population and just over 50% of an estimated population of 127 000 were seen in the areas visited by the teams. The non-Aboriginal population was to a certain extent selfselected and no attempt was made to obtain comprehensive coverage. A detailed account of methods, diagnostic criteria, and data handling has appeared elsewhere.3 The mainland of Australia was divided into five ultraviolet zones4 (see accompanying figure). Cataract prevalence was tested against UV zone and the vision of persons with cataract was noted. Good vision was defined as 6/12 or better in the better eye; poor vision as 6/36, 6/24, or 6/18 in the better eye; and blindness as vision 6/60 or worse in the better eye. Contingency table analysis, logit analysis, and the X2 test were used as the tests of statistical significance. For convenience, p values
Zones of ultraviolet radiation in Australia expressed units of UVB daily (average).
statistically significant (p<0. 001). Non-Aborigines aged over 60 years with cataract were less likely to be blind or have poor vision than their Aboriginal counterparts (table II) (p<0-001). For non-Aborigines, the overall prevalence of cataract for the over 60s was just under two-thirds of the corresponding Aboriginal prevalence. For the younger agegroup, however, the non-Aboriginal prevalence was one-fifth to one-sixth of that for Aborigines (table III). Cataract in nonAborigines was associated with less visual loss; 10% of the 958 over 60 year olds with this diagnosis were blind and another 37% had poor vision (table II). No significant correlation between cataract prevalence and UV zone was found for non-Aborigines and there was no significant sex
difference. TABLE I-CATARACT PREVALENCE IN ABORIGINES BY ULTRAVIOLET
ZONE
n= population examined in this age-group. TABLE II-VISION IN ABORIGINES OVER
60 YEARS
WITH CATARACT BY
ULTRAVIOLET ZONE AND IN NON-ABORIGINES WITH CATARACT, ALL ZONES
Results There was a significant positive correlation between climatic UV irradiation and cataract prevalence (p<0. 005), (table I). In addition there was a disproportionate increase in in the younger age-group (40-59) with UV In zone 1 (least irradiation increasing (p<0-005). irradiation), 1 -.7% of the 58 Aborigines between 40-59 years had cataract. In zone 5, 5-1% of this cohort had cataract.
erythemal
No significant sex difference was found overall, or in any of the UV zones, in Aborigines for cataract. Aborigines over the age of 60 years who had cataract were much more likely to be blind or have poor vision if they lived in a zone of high UV irradiation (table II). This trend was
only are shown.
cataract
as
prevalence
Where percentages do
not
total 100%, vision
was not
recorded.
1250
1 l-tf.LrCi,L’IttHVH}t!.KJ, 1’011
TABLE III-COMPARISON OF NON-ABORIGINAL AND ABORIGINAL
CATARACT PREVALENCE
We thank Prof. C. McGilchrist and his department for statistical advice; Dr David Jones; and Ms L. Greenaway. The National Trachoma and Eye Health Program is an independent programme of the Royal Australian College of Ophthalmologists, funded and supported by the Commonwealth Department of Health. Conclusions drawn and recommendations made here are not necessarily those of the Royal Australian College of Ophthalmologists or of the Commonwealth Department of Health. The programme acknowledges the cooperation and assistance of the health departments of New South Wales, Victoria, Northern Territory, Queensland, South Australia, and Western Australia.
Correspondence should be addressed to D. M., Department of Ophthalmology, Prince of Wales Hospital, High Street, Randwick, N.S.W. 2031, Australia.
Discussion
Aboriginal Australians form a significant proportion of the population of the more arid parts of the continent and, unlike their White counterparts, were likely to have spent most of their lives in the geographical area in which they were examined. Their lifestyle tends to be uniform, in that most Aboriginal communities share to a great extent the health and social problems which invariably occur in dispossessed peoples. They live largely in makeshift housing on bare unshaded ground and spend most of their lives out-of-doors, either in their tribal homelands, or as fringe-dwellers. This exposes them to high levels of solar radiation for many hours each day. Ultraviolet radiation in particular is scattered in the atmosphere by the Rayleigh effect so that shade from trees or hats affords the eyes only partial protection. Thus, Aborigines in remote rural Australia form a suitable population, with an outdoor lifestyle and consistent socioeconomic circumstances, in which to test the effect of climatic variables such as UV radiation. Because Aboriginal communities have been and continue to be underserviced by ophthalmic and other health professions and because we obtained a good population coverage, the point prevalence of cataract is likely to be reliable and little affected by surgical intervention. Non-Aboriginal people seen in the same regions were much less likely to have lived all their lives in that area, were more likely to have indoor occupations, and were almost certain to be adequately housed and serviced, with a high standard of living. We feel this explains the lack of correlation between insolation and cataract prevalence in this population. We have demonstrated that solar UV radiation increases cataract prevalence in Aborigines in Australia. We have little information, however, on other factors which may influence cataract prevalence. For example, the effect of carbohydrate intolerance is unknown, and the extent to which it, solar radiation, and ageing are linked is yet to be determined. Epidemiological studies of cataract prevalence by Zigman5 et al. and Hiller6 at different latitudes and in areas of varying insolation have indicated a relation between cataract prevalence and high sunshine intensity. More recently, Taylor’ found a significant correlation with UV irradiation in a sample of Aborigines in Central Australia. Chatterjee,8 in a study of 20 000 people in the Punjab, found a higher prevalence of cataract than did McWilliam9 in Scotland, where UV levels are much lower. However, the effects of racial and nutritional differences in these studies are not known. Our data, taken on a nationwide basis, confirm the relation and show, in addition, that cataract develops earlier in life and also has more severe visual consequences in areas of high UV radiation. The prevention of cataract may be another compelling reason for the provision of good housing in tropical and arid regions of the world. The use of sunglasses by people at risk may also be helpful.
REFERENCES 1. Pirie A. Photo-oxidation of proteins and comparison of photo-oxidation proteins with those of the cataractous human lens. Israel J Med Sci 1972; 8: 1567-73. 2. Zigman S. Ocular protein alterations by near ultraviolet light. Exp Eye Res 1973, 15: 253-64. 3. Report of the National Trachoma and Eye Health Program, Royal Australian College of Ophthalmologists, Sydney 1980; ISBN 0 9594785 0 7. 4. Paltridge GW, Barton IJ. Erythemal ultraviolet radiation distribution over Australia-the calculations, detailed results and input data including frequency analysis of observed Australian cloud cover. CSIRO, Division of Atmospheric Physics Technical Paper (No. 33), Sydney, 1978. 5. Zigman S, Datiles M, Torczynski E. Sunlight and human cataracts. Invest Ophthalmol Vis Sci 1979; 18: 462-67. 6. Hiller H. Sunlight and cataract. Am J Epidemiol 1977; 5: 450-59. 7. Taylor HR. The environment and the lens. Br J Ophthalmol 1980; 64: 303-10. 8. Chatterjee J. Cataract in the Punjab. In: Symposium on the human lens in relation to cataract. Ciba Foundation Symposium 19 (new series) Amsterdam, Associated Scientific Publishers. 1973; 265-79. 9. McWilliam RJ. Ophthalmological results of a geriatric assessment survey. Trans Ophthalmol Soc UK 1975; 95: 71.
THERAPEUTIC SELECTIVITY OF AND PREDICTION OF RESPONSE TO 2’-DEOXYCOFORMYCIN IN ACUTE LEUKAEMIA N. H. RUSSELL K. GANESHAGURU A. PIGA A. V. HOFFBRAND
H. G. PRENTICE N. LEE H. BLACKLOCK J. F. SMYTH
Department of Haematology, Royal Free Hospital and Medical School, London, and Department of Clinical Oncology, Western General Hospital, Edinburgh with acute leukaemia chemotheraconventional refractory adenosine deaminase were treated with the peutic agents inhibitor, 2’-deoxycoformycin (dCF). Of the twelve patients with acute lymphoblastic leukaemia of the thymic phenotype (Thy-ALL), seven went into complete remission after one or two courses of therapy. Two other (Thy-ALL) patients showed good partial response, and three were resistant to dCF. The five patients with acute leukaemia of other phenotypes had progression of disease despite treatment with dCF. Response to dCF can be predicted from the pattern of change in cellular nucleotide levels in blood and/or bone marrow blasts which have been treated in vitro with dCF and deoxyadenosine. The main adverse effects of dCF therapy were renal and liver dysfunction, conjunctivitis, and
Summary
Seventeen
patients to
haemolysis. Introduction A RELAPSE of
leukaemia carries a poor prognosis. who patients relapse while on maintenance chemotherapy subsequently die from the disease. 1,2 Those who do not are usually those who have had ablative acute
Almost all
chemoradiotherapy, followed by allogeneic
or
syngeneic
FRED HOLLOWS
Department of Ophthalmology, Prince of Wales Hospital/University of New South Wales, Australia
Ophthalmic examination of 64 307 Aborigines and 41 254 non-Aborigines in remote rural Australia during the course of the National Trachoma and Eye Health Program revealed a positive correlation between the prevalence of senile cataract and levels of climatic ultraviolet (UV) radiation. Aborigines were more likely to be affected by senile cataract than nonAborigines. It seems that Aborigines who live in areas of higher UV irradiation are more likely to acquire cataract; more likely to acquire the condition earlier in life; and more likely to be blind or visually disabled by it, than their counterparts living in areas of low UV irradiation. Provision of adequate shelter in areas of high insolation, where most cases of cataract occur, is likely to be an effective preventive Summary
measure.
Introduction NEAR ultraviolet (UV) light is able to induce opacity of the crystalline lens, both in vivo and in vitro. This process probably involves the photoxidation of aromatic aminoacids, particularly tryptophan. n2 The effect seems to be cumulative and is inhibited by physiological levels of ascorbate and glutathione, a fact which provides an enticing clue to the specific functions of these two substances in the lens. Our data on more than 105 000 people examined in more than 400 centres throughout the more remote parts of the Australian continent presented an opportunity to assess cataract prevalence and effects in the two major racial groups living in a range of different zones of UV irradiation. Methods
Ophthalmologists from the National Trachoma and Eye Health Program examined 64 307 Aborigines and 41 254 non-Aborigines during the course of three years’ fieldwork. An attempt was made to obtain a thorough coverage of the Aboriginal population and just over 50% of an estimated population of 127 000 were seen in the areas visited by the teams. The non-Aboriginal population was to a certain extent selfselected and no attempt was made to obtain comprehensive coverage. A detailed account of methods, diagnostic criteria, and data handling has appeared elsewhere.3 The mainland of Australia was divided into five ultraviolet zones4 (see accompanying figure). Cataract prevalence was tested against UV zone and the vision of persons with cataract was noted. Good vision was defined as 6/12 or better in the better eye; poor vision as 6/36, 6/24, or 6/18 in the better eye; and blindness as vision 6/60 or worse in the better eye. Contingency table analysis, logit analysis, and the X2 test were used as the tests of statistical significance. For convenience, p values
Zones of ultraviolet radiation in Australia expressed units of UVB daily (average).
statistically significant (p<0. 001). Non-Aborigines aged over 60 years with cataract were less likely to be blind or have poor vision than their Aboriginal counterparts (table II) (p<0-001). For non-Aborigines, the overall prevalence of cataract for the over 60s was just under two-thirds of the corresponding Aboriginal prevalence. For the younger agegroup, however, the non-Aboriginal prevalence was one-fifth to one-sixth of that for Aborigines (table III). Cataract in nonAborigines was associated with less visual loss; 10% of the 958 over 60 year olds with this diagnosis were blind and another 37% had poor vision (table II). No significant correlation between cataract prevalence and UV zone was found for non-Aborigines and there was no significant sex
difference. TABLE I-CATARACT PREVALENCE IN ABORIGINES BY ULTRAVIOLET
ZONE
n= population examined in this age-group. TABLE II-VISION IN ABORIGINES OVER
60 YEARS
WITH CATARACT BY
ULTRAVIOLET ZONE AND IN NON-ABORIGINES WITH CATARACT, ALL ZONES
Results There was a significant positive correlation between climatic UV irradiation and cataract prevalence (p<0. 005), (table I). In addition there was a disproportionate increase in in the younger age-group (40-59) with UV In zone 1 (least irradiation increasing (p<0-005). irradiation), 1 -.7% of the 58 Aborigines between 40-59 years had cataract. In zone 5, 5-1% of this cohort had cataract.
erythemal
No significant sex difference was found overall, or in any of the UV zones, in Aborigines for cataract. Aborigines over the age of 60 years who had cataract were much more likely to be blind or have poor vision if they lived in a zone of high UV irradiation (table II). This trend was
only are shown.
cataract
as
prevalence
Where percentages do
not
total 100%, vision
was not
recorded.
1250
1 l-tf.LrCi,L’IttHVH}t!.KJ, 1’011
TABLE III-COMPARISON OF NON-ABORIGINAL AND ABORIGINAL
CATARACT PREVALENCE
We thank Prof. C. McGilchrist and his department for statistical advice; Dr David Jones; and Ms L. Greenaway. The National Trachoma and Eye Health Program is an independent programme of the Royal Australian College of Ophthalmologists, funded and supported by the Commonwealth Department of Health. Conclusions drawn and recommendations made here are not necessarily those of the Royal Australian College of Ophthalmologists or of the Commonwealth Department of Health. The programme acknowledges the cooperation and assistance of the health departments of New South Wales, Victoria, Northern Territory, Queensland, South Australia, and Western Australia.
Correspondence should be addressed to D. M., Department of Ophthalmology, Prince of Wales Hospital, High Street, Randwick, N.S.W. 2031, Australia.
Discussion
Aboriginal Australians form a significant proportion of the population of the more arid parts of the continent and, unlike their White counterparts, were likely to have spent most of their lives in the geographical area in which they were examined. Their lifestyle tends to be uniform, in that most Aboriginal communities share to a great extent the health and social problems which invariably occur in dispossessed peoples. They live largely in makeshift housing on bare unshaded ground and spend most of their lives out-of-doors, either in their tribal homelands, or as fringe-dwellers. This exposes them to high levels of solar radiation for many hours each day. Ultraviolet radiation in particular is scattered in the atmosphere by the Rayleigh effect so that shade from trees or hats affords the eyes only partial protection. Thus, Aborigines in remote rural Australia form a suitable population, with an outdoor lifestyle and consistent socioeconomic circumstances, in which to test the effect of climatic variables such as UV radiation. Because Aboriginal communities have been and continue to be underserviced by ophthalmic and other health professions and because we obtained a good population coverage, the point prevalence of cataract is likely to be reliable and little affected by surgical intervention. Non-Aboriginal people seen in the same regions were much less likely to have lived all their lives in that area, were more likely to have indoor occupations, and were almost certain to be adequately housed and serviced, with a high standard of living. We feel this explains the lack of correlation between insolation and cataract prevalence in this population. We have demonstrated that solar UV radiation increases cataract prevalence in Aborigines in Australia. We have little information, however, on other factors which may influence cataract prevalence. For example, the effect of carbohydrate intolerance is unknown, and the extent to which it, solar radiation, and ageing are linked is yet to be determined. Epidemiological studies of cataract prevalence by Zigman5 et al. and Hiller6 at different latitudes and in areas of varying insolation have indicated a relation between cataract prevalence and high sunshine intensity. More recently, Taylor’ found a significant correlation with UV irradiation in a sample of Aborigines in Central Australia. Chatterjee,8 in a study of 20 000 people in the Punjab, found a higher prevalence of cataract than did McWilliam9 in Scotland, where UV levels are much lower. However, the effects of racial and nutritional differences in these studies are not known. Our data, taken on a nationwide basis, confirm the relation and show, in addition, that cataract develops earlier in life and also has more severe visual consequences in areas of high UV radiation. The prevention of cataract may be another compelling reason for the provision of good housing in tropical and arid regions of the world. The use of sunglasses by people at risk may also be helpful.
REFERENCES 1. Pirie A. Photo-oxidation of proteins and comparison of photo-oxidation proteins with those of the cataractous human lens. Israel J Med Sci 1972; 8: 1567-73. 2. Zigman S. Ocular protein alterations by near ultraviolet light. Exp Eye Res 1973, 15: 253-64. 3. Report of the National Trachoma and Eye Health Program, Royal Australian College of Ophthalmologists, Sydney 1980; ISBN 0 9594785 0 7. 4. Paltridge GW, Barton IJ. Erythemal ultraviolet radiation distribution over Australia-the calculations, detailed results and input data including frequency analysis of observed Australian cloud cover. CSIRO, Division of Atmospheric Physics Technical Paper (No. 33), Sydney, 1978. 5. Zigman S, Datiles M, Torczynski E. Sunlight and human cataracts. Invest Ophthalmol Vis Sci 1979; 18: 462-67. 6. Hiller H. Sunlight and cataract. Am J Epidemiol 1977; 5: 450-59. 7. Taylor HR. The environment and the lens. Br J Ophthalmol 1980; 64: 303-10. 8. Chatterjee J. Cataract in the Punjab. In: Symposium on the human lens in relation to cataract. Ciba Foundation Symposium 19 (new series) Amsterdam, Associated Scientific Publishers. 1973; 265-79. 9. McWilliam RJ. Ophthalmological results of a geriatric assessment survey. Trans Ophthalmol Soc UK 1975; 95: 71.
THERAPEUTIC SELECTIVITY OF AND PREDICTION OF RESPONSE TO 2’-DEOXYCOFORMYCIN IN ACUTE LEUKAEMIA N. H. RUSSELL K. GANESHAGURU A. PIGA A. V. HOFFBRAND
H. G. PRENTICE N. LEE H. BLACKLOCK J. F. SMYTH
Department of Haematology, Royal Free Hospital and Medical School, London, and Department of Clinical Oncology, Western General Hospital, Edinburgh with acute leukaemia chemotheraconventional refractory adenosine deaminase were treated with the peutic agents inhibitor, 2’-deoxycoformycin (dCF). Of the twelve patients with acute lymphoblastic leukaemia of the thymic phenotype (Thy-ALL), seven went into complete remission after one or two courses of therapy. Two other (Thy-ALL) patients showed good partial response, and three were resistant to dCF. The five patients with acute leukaemia of other phenotypes had progression of disease despite treatment with dCF. Response to dCF can be predicted from the pattern of change in cellular nucleotide levels in blood and/or bone marrow blasts which have been treated in vitro with dCF and deoxyadenosine. The main adverse effects of dCF therapy were renal and liver dysfunction, conjunctivitis, and
Summary
Seventeen
patients to
haemolysis. Introduction A RELAPSE of
leukaemia carries a poor prognosis. who patients relapse while on maintenance chemotherapy subsequently die from the disease. 1,2 Those who do not are usually those who have had ablative acute
Almost all
chemoradiotherapy, followed by allogeneic
or
syngeneic